Skin Cancer Risk of Narrow-Band UV-B (TL-01) Phototherapy: A Multi-Center Registry Study with 4,815 Patients.

Narrow-band TL-01 ultraviolet B phototherapy (TL-01) is an effective and widely used treatment for many skin diseases. The purpose of the investigation was to assess the risk of skin cancers in patients treated with TL-01 phototherapy who have not received any other phototherapy modalities. This cohort study included 4,815 TL-01 treated patients in Finland with psoriasis or atopic dermatitis. Clinical information was collected from the hospital records and linked with Finnish Cancer Registry data. The follow-up started from the first TL-01 treatment and the mean follow-up time was 8.4 years. Standardized incidence ratios were calculated for basal cell carcinoma, cutaneous melanoma, and squamous cell carcinoma. The standardized incidence ratio for basal cell carcinoma was 2.5 (95% confidence interval 1.8-3.5), for cutaneous melanoma 4.0 (95% confidence interval 2.1-6.8) and for squamous cell carcinoma 3.7 (95% confidence interval 1.7-7.0). For basal cell carcinoma and squamous cell carcinoma, the standardized incidence ratios remained similar during the whole follow-up time while the standardized incidence ratio for cutaneous melanoma was markedly higher during the first 5 years of follow-up. In conclusion, an increased incidence of skin cancers was observed among TL-01 treated patients. It should be confirmed in the future whether the skin cancer risk of TL-01 phototherapy will remain high in a longer follow-up.

Genetic predisposition to childhood obesity does not influence the risk of developing skin cancer in adulthood.

The relationship between body mass index (BMI) and melanoma and other skin cancers remains unclear. The objective of this study was to employ the Mendelian randomization (MR) approach to evaluate the effects of genetically predicted childhood adiposity on the risk of developing skin cancer later in life. Two-sample MR analyses were conducted using summary data from genome-wide association study (GWAS) meta-analyses of childhood BMI, melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). We used the inverse-variance-weighted (IVW) methods to obtain a pooled estimate across all genetic variants for childhood BMI. We performed multiple sensitivity analyses to evaluate the potential influence of various assumptions on our findings. We found no evidence that genetically predicted childhood BMI was associated with risks of developing melanoma, cSCC, or BCC in adulthood (OR, 95% CI: melanoma: 1.02 (0.93-1.13), cSCC 0.94 (0.79-1.11), BCC 0.97 (0.84-1.12)). Our findings do not support the conclusions from observational studies that childhood BMI is associated with increased risks of melanoma, cSCC, or BCC in adulthood. Intervening on childhood adiposity will not reduce the risk of common skin cancers later in life.

Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma.

BACKGROUND AND OBJECTIVES: Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro-photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet-induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS-development. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time-period of 7 years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus. RESULTS: Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients. CONCLUSIONS: This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.

Excision pathways for keratinocyte cancers diagnosed by teledermatology: a retrospective review.

Introduction The New Zealand population has one of the highest incidences of skin cancer in the world. Hospital waiting lists for surgical excision of keratinocytic skin cancers (basal cell carcinoma and squamous cell carcinoma) are lengthy, and increasingly, excisions are undertaken in primary care. Teledermatology, in response to general practitioners' electronic referrals (e-referrals), can improve clinical communication between general practitioners and dermatologists. Aim The aim of this study was to evaluate an excision pathway for keratinocytic cancers diagnosed by teledermatology. Methods A retrospective observational descriptive review of a 3-month cohort of primary care e-referrals was undertaken. Results Three hundred and fifty eight suspected keratinocytic cancers (KCs) were diagnosed by teledermatology; histology reports confirmed KC in 201 of 267 excisions (75%). The majority (77.2%) were excised by general practitioners an average of 25 days after the dermatologist's recommendation. The rest were excised by plastic surgeons in private (3.4%) or at a public hospital (19.5%) after an average of 40 or 134 days, respectively. Discussion E-referral pathways are now widely implemented. However, the ideal workflow for skin cancer management is unknown. We have demonstrated in New Zealand that surgery can be undertaken in primary care within a month of a teledermatology diagnosis and excision recommendation. Conclusion This study reports prompt excision of KCs by general practitioners after an e-referral and a teledermatology response.

Spectrum of malignant and premalignant skin lesions in 505 adult subjects at risk of skin cancers.

Patients at risk of skin cancers can develop varying types of cutaneous malignancies. However, some subjects may develop only one type of lesion. In this cross-sectional study, the spectrum of premalignant (PM) and malignant skin lesions and their risk factors were studied. Therefore, 505 adult subjects (aged 21-79 years, 256 males and 249 females, 96 with immunosuppression) at risk of any type of skin cancer were examined for cutaneous malignancies, nevi, actinic keratoses, photodamage, and possible risk factors. First, 12 different groups were identified with a varying set of PM and/or malignant skin lesions. Next, 5 larger groups were formed from them: basal cell carcinoma (BCC) only, malignant melanoma (MM) only, squamous cell carcinoma (SCC) and/or PM, BCC + SCC and/or PM, and MM + keratinocyte carcinoma (KC) and/or PM. The groups with BCC or MM only were younger and showed less photodamage than the mixed groups, while SCC/PM showed similarity with them. In logistic regression analyses, the platelet-to-lymphocyte ratio was associated with an increased risk of concomitant KC (OR 1.028, p = 0.023) or SCC/PM (OR 1.009, p = 0.047) in subjects with MM or BCC, respectively. Actinic keratoses produced ORs 0.246-0.252 (p = 0.008-0.020) for BCC in subjects with SCC/PM. Interestingly, atypical mole syndrome decreased the risk of SCC/PM in subjects with BCC (OR 0.092, p = 0.001). Advanced age was a significant risk factor for an additional type of lesion in all 3 comparisons (ORs 1.088-1.388, p = 0.001). In conclusion, even though there are numerous patients with only one lesion type, advancing age may determine the final lesion multiplicity.

Incidence and survival rates of primary cutaneous malignancies in Korea, 1999-2019: A nationwide population-based study.

Primary cutaneous malignancies are among the most commonly diagnosed types of cancer worldwide. We aimed to examine the incidence and 5-year survival rates of all types of primary cutaneous malignancies in the Korean population. Data from the Korean Nationwide Cancer Registry from 1999 to 2019 were analyzed. The crude incidence rates, age-standardized incidence rates, and 5-year relative survival rates of each type of skin cancer were calculated. A total of 89 965 patients were diagnosed with primary cutaneous malignancies, which was a 7-fold increase from 1999 to 2019. The age-standardized incidence rates increased 3.4-fold in basal cell carcinoma (3.7/100 000 person-years), 2.0-fold in squamous cell carcinoma (1.6/100 000 person-years), 12.0-fold in Bowen disease (1.2/100 000 person-years), and 1.8-fold in malignant melanoma (0.7/10 000 person-years) in 2019. Average annual percentage changes in age-standardized incidence rates were statistically significant in basal cell carcinoma (15.8%), Bowen disease (5.8%), squamous cell carcinoma (5.1%), malignant melanoma (1.2%), melanoma in situ (1.1%), dermatofibrosarcoma protuberans (1.2%), mycosis fungoides (0.5%), primary cutaneous CD30+ T-cell proliferations (0.5%), adnexal and skin appendage carcinoma (0.4%), extramammary Paget's disease (0.2%), and Merkel cell carcinoma (0.2%). The 5-year relative survival rates were the highest in basal cell carcinoma (103.3%), followed by dermatofibrosarcoma protuberans (99.7%) and mycosis fungoides (96.6%), and lowest in angiosarcoma (24.7%). The 5-year relative survival rates steadily increased in extramammary Paget's disease (23.6%), cutaneous B-cell lymphoma (21.3%), mycosis fungoides (20.2%), extranodal NK/T-cell lymphoma, nasal type (18.1%), and malignant melanoma (16.1%) from 1996-2000 to 2015-2019. Most primary cutaneous malignancies have increased in incidence and survival rates in the Korean population, but to varying extents depending on the type of skin cancer.

Does the risk of basal cell carcinoma increase in patients with psoriasis under treatment?

BACKGROUND: Psoriasis is a common, chronic, inflammatory disease. Although it mainly affects the skin, it has been associated with a large number of comorbidities. In addition to comorbidities such as depression and psoriatic arthritis, it is known that there is an increased prevalence of cancer in psoriasis patients. Skin cancers, particularly squamous cell carcinoma, have been associated with psoriasis. However, basal cell carcinoma data are limited. METHODS: 346 psoriasis patients and 306 individuals were selected as the control group. There were no differences between the patient and control groups in terms of age and gender. The mean age of the psoriasis patients was 49.9 ± 15.8 years and the control group was 49.4 ± 13.4 years. Sociodemographic data of the patients were recorded. Pharmacological agents used in the treatment of psoriasis were included in the analysis. Disease severity was assessed by the psoriasis area severity index (PASI). In the physical examination of the patients, biopsies were taken from lesions suspicious for BCC. BCC diagnosis was made by histopathologically. RESULTS: The frequency of BCC was higher in psoriasis patients than in the control group (6.6% vs. 2.9%, p < .001). Advanced age (p < .001), smoking (p = .003), and arthritis (p < .001) were associated with BCC in psoriasis patients. However, there was no relationship between PASI and BCC (p = .142). Among the psoriasis treatments, only UV therapy was associated with BCC (p = .038). The frequency of PUVA (p < .001) and number of PUVA session (p = .010) was higher in psoriasis patients with BCC rather than NB-UVB. CONCLUSION: The frequency of BCC is increased in psoriasis patients. Psoriasis is associated with an increased risk of BCC, especially when treated with PUVA therapy for a long time.

Removal of Incidental Skin Cancer During Mohs Micrographic Surgery Indicated for a Different Primary Tumor.

BACKGROUND: Mohs surgery is a tissue-sparing, microscopically controlled procedure used to treat biopsy-proven skin cancers. Because Mohs surgery allows for examination of the complete margin of each tissue layer removed, separate cancers can be treated concomitantly when identified. As early detection of skin cancer is beneficial for reducing morbidity, incidental tumors discovered during Mohs surgery are of significant interest. OBJECTIVE: Our objective was to determine the prevalence and characteristics of incidental skin cancers found during Mohs surgery. METHODS: A retrospective chart review of cases seen at University of California, San Diego, from 2014 to 2021 was performed. RESULTS: Of 13,464 Mohs surgery cases, 4.53% ( n = 610) had incidental skin cancers found during removal of the initially identified tumor. Of the 610 cases, 88.4% ( n = 539) had basal cell carcinoma as the primary tumor and either squamous cell carcinoma (SCC) or SCC in situ as the incidental tumor. About 7.87% ( n = 48) had SCC as the primary tumor and basal cell carcinoma as the incidental tumor. All tumors were removed with clear margins and without significant complications. CONCLUSION: Diagnosis of incidental tumors during Mohs surgery enables early detection of skin cancer and circumvents the need for additional surgery, likely resulting in decreased morbidity and improved cost-effectiveness.

Occupational solar exposure and basal cell carcinoma. A review of the epidemiologic literature with meta-analysis focusing on particular methodological aspects.

BACKGROUND: Numerous epidemiologic studies and a few systematic reviews have investigated the association between occupational solar exposure and basal cell carcinoma (BCC). However, previous reviews have several deficits with regard to included and excluded studies/risk estimates and the assessment of risk of selection bias (RoSB). Our aim was to review epidemiologic studies with a focus on these deficits and to use meta-(regression) analyses to summarize risk estimates. METHODS: We systematically searched PubMed (including MEDLINE) and Embase for epidemiologic studies. Study evaluation considered four main aspects of risk of bias assessments, i.e. Selection of subjects (selection bias); Exposure variables; Outcome variables; Data analysis. RESULTS: Of 56 identified references, 32 were used for meta-(regression) analyses. The overall pooled risk estimate for BCC comparing high/present vs. low/absent occupational solar exposure was 1.20 (95% CI 1.02-1.43); among studies without major deficits regarding data analysis, it was 1.10 (95% CI 0.91-1.33). Studies with low and high RoSB had pooled risk estimates of 0.83 (95% CI 0.73-0.93) and 1.95 (95% CI 1.42-2.67), respectively. The definitions of exposure and outcome variables were not correlated with study risk estimates. Studies with low RoSB in populations with the same latitude or lower than Germany had a pooled risk estimate of 1.01 (95% CI 0.88-1.15). CONCLUSION: Due to the different associations between occupational solar exposure and BCC among studies with low and high RoSB, we reason that the current epidemiologic evidence base does not permit the conclusion that regular outdoor workers have an increased risk of BCC.

PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico.

BACKGROUND: Basal cell carcinoma (BCC) represents about 80% of all cases of skin cancer. The PTCH1 is a transmembrane protein of the Sonic Hedgehog signaling pathway that regulates cell proliferation. Genetic variants in PTCH1 gene have been previously described in association with BCC development. In addition, PTCH1 mRNA and protein expression analysis are also significant to understand its role in skin cancer physiopathology. METHODS: An analytical cross-sectional study was performed, and a total of 250 BCC patients and 290 subjects from the control group (CG) were included, all born in western Mexico. The genotypes and relative expression of the mRNA were determined by TaqMan® assay. The protein expression was investigated in 70 BCC paraffin-embedded samples with PTCH1 antibodies. Semi-quantitative analysis was performed to determine the expression level in the immunostained cells. RESULTS: We did not find evidence of an association between PTCH1 rs357564, rs2297086, rs2236405, and rs41313327 genetic variants and susceptibility to BCC. Likewise, no statistically significant differences were found in the comparison of the mRNA level expression between BCC and CG (p > 0.05). The PTCH1 protein showed a low expression in 6 of the analyzed samples and moderate expression in 1 sample. No association was found between genetic variants, protein expression, and demographic-clinical characteristics (p > 0.05). CONCLUSION: The studied PTCH1 variants may not be associated with BCC development in the Western Mexico population. The PTCH1 mRNA levels were lower in patients with BCC compared to the control group, but its protein was underexpressed in the tissue samples.

Non-melanoma skin cancer event rates in a formalized clinical trial setting: considerations for clinical trial design.

BACKGROUND: Here we report clinical risk factors and event rates for the development of new non-melanoma skin cancer (NMSC) in a randomized, double-blind, placebo-controlled trial of the irreversible ornithine decarboxylase (ODC) inhibitor, difluromethylornithine (DFMO), over a 3-5-year follow-up. METHODS: 147 placebo patients (white; mean age 60.2 years; 60% male) were evaluated for event rates and association of initial skin biomarkers and baseline patient characteristics with the development of squamous cell (SCC) and basal cell (BCC) carcinomas. RESULTS: Post-study evaluation (median follow-up 4.4 years) indicates the measures of prior NMSCs ( P  ≤ 0.001), prior BCCs ( P  ≤ 0.001), prior SCCs ( P  = 0.011), prior tumor rate ( P  = 0.002), hemoglobin ( P  = 0.022), and gender ( P  = 0.045) as significant predictors for new NMSC development. Similarly, all measures of prior BCCs and NMSCs ( P  < 0.001), prior tumor rate ( P  = 0.014), and SCCs in the prior 2 years ( P  = 0.047) were statistically significant predictors for new BCC development. Total prior NMSCs and those in the prior 5 years ( P  < 0.001), total prior SCCs and those in the prior 5 years ( P  < 0.001), total prior BCCs and those in the prior 5 years ( P  ≤ 0.001), prior tumor rate ( P  = 0.011) as well as age ( P  = 0.008), hemoglobin ( P  = 0.002), and gender ( P  = 0.003) were statistically significant predictors of new SCC development. TPA-induced ODC activity at baseline showed no statistically significant association with the development of new NMSC ( P  = 0.35), new BCCs ( P  = 0.62), or new SCCs ( P  = 0.25). CONCLUSION: In the studied population, the history of and rate at which prior NMSCs occur are predictive and should be controlled for in future NMSC prevention trials.

Comparison of the clinical characteristics of benign and malignant eyelid lesions: an analysis of 1423 eyelid lesions, compared between ophthalmology department and plastics department.

PURPOSE: Oculoplastic surgeons excise and reconstruct eyelid tumors, although plastic surgeons have traditionally managed these cases. Current demand of this surgery is growing, and planning referral services is a health management necessity. This pilot study retrospectively reviewed same population eyelid specimens excised by both disciplines comparing data. METHODS: Clinical and epidemiologic features of 1423 eyelid lesions biopsied between 2015- 2020 in Emek Medical Center (EMC), Israel were reviewed. RESULTS: Among 1423 specimens, 1210 (85.0%) were benign and 213 (15.0%) were malignant/pre-malignant. Mean age at diagnosis was significantly higher in malignant tumors than in benign tumors (76 and 59 years respectively, p value < 0.001). The most common benign eyelid lesions were soft fibroma (20.1%), seborrheic keratosis (11.0%) and melanocytic nevus (10.3%). The most common malignant/pre-malignant eyelid tumors were basal cell carcinoma (BCC) (9.2%), actinic keratosis (2.6%) and Bowen's disease (1.9%). Ophthalmology removed 37 malignant/pre-malignant lesions (5.4%) out of 683 compared to plastics removing 142 malignant/pre-malignant lesions out of 740 (19.2%) specimens. Eyelid malignancy in the plastics department was significantly higher than in the ophthalmology department (p value < 0.001). 270 (70.0%) lesions caused by UV exposure were removed by plastics and 116 (30.0%) were removed by ophthalmology (p value < 0.001). CONCLUSIONS: Eyelid lesions in patients aged 76 or older are more likely to be malignant. Ophthalmology eyelid specimens in younger patients are more commonly benign and related to inflammation. Specimens from the plastics department are more commonly malignant, related to UV-exposure, and are from older patients. This difference may be due to a misconception that plastic surgeons have more eyelid cancer reconstruction experience than oculoplastic surgeons, or less awareness of the oculoplastic expertise available today.

Survival of patients with basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ: A whole population study.

BACKGROUND: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood. OBJECTIVES: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders. METHODS: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015. RESULTS: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis. CONCLUSION: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups.

Skin Cancers in Medicare Beneficiaries With Actinic Keratoses.

Importance: Actinic keratoses (AK) are common premalignant skin lesions with a small risk of progressing to cutaneous squamous cell carcinoma (SCC). There is some evidence that patients with AKs also have increased risks of other skin cancers beyond SCC. However, the absolute risks of skin cancer in patients with AKs are unknown. Objective: To calculate the absolute and relative risks of future skin cancer in Medicare beneficiaries with AKs. Design, Setting, and Participants: This retrospective cohort study was performed using a deidentified, random sample of 4 999 999 fee-for-service Medicare beneficiaries from 2009 through 2018. Patients with treated AKs were included, and patients with seborrheic keratoses (SKs) were included as a comparator group. All patients were required to have at least 1 year between data set entry and first AK or SK. Patients with a history of skin cancer were excluded. Data were analyzed from September 2022 to March 2023. Main Outcomes and Measures: Outcomes were first surgically treated skin cancer, including keratinocyte carcinoma (including SCC and basal cell carcinoma [BCC]) and melanoma. The absolute risks of skin cancer in patients with AKs were evaluated. Skin cancer risks in patients with AKs were compared with patients with SKs using adjusted competing risks regression. Results: A total of 555 945 patients with AKs (mean [SD] age, 74.0 [7.4] years; 55.4% female) and 481 024 patients with SKs (mean [SD] age, 73.3 [7.3] years; 72.4% female) were included. The absolute risk of skin cancer after a first AK was 6.3% (95% CI, 6.3%-6.4%) at 1 year, 18.4% (95% CI, 18.3%-18.5%) at 3 years, and 28.5% (95% CI, 28.4%-28.7%) at 5 years. Patients with AKs had increased risk of skin cancer compared with patients with SKs (any skin cancer: adjusted hazard ratio [aHR], 2.17; 95% CI, 2.15-2.19; keratinocyte carcinoma: aHR, 2.20; 95% CI, 2.18-2.22; SCC: aHR, 2.63; 95% CI, 2.59-2.66; BCC: aHR, 1.85; 95% CI, 1.82-1.87; and melanoma: aHR, 1.67; 95% CI, 1.60-1.73). Conclusions and Relevance: In this cohort study, older patients with AKs had substantial absolute risks, as well as elevated relative risks, of skin cancer. AKs may be clinical markers of UV exposure and increased skin cancer risk, including SCC, BCC, and melanoma. However, guidelines are lacking for follow-up skin cancer surveillance in patients with AKs. Efforts to develop evidence-based recommendations for skin cancer surveillance in patients with AKs are paramount.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

Evaluating the effect of body mass index and 25-hydroxy-vitamin D level on basal cell carcinoma using Mendelian randomization.

Basal cell carcinoma (BCC) is the most common cancer with a rising incidence among white-skinned individuals. A number of epidemiological studies have suggested that obesity and serum 25-hydroxy-vitamin D (25(OH)D) levels may affect the arising of BCC. To address this, we selected 443 and 96 single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and serum level of 25(OH)D from large-scale genome-wide association studies (GWAS), respectively. The univariable and multivariable two-sample Mendelian randomization (MR) analyses were conducted with a series of sensitivity analyses to ensure the results were reliable and reproducible. The results of univariable two-sample MR analysis showed that higher BMI was related to lower risk for BCC (Odds ratio(OR) = 0.90; 95% confidence interval (CI),[0.81,0.99]; p = 0.02). In addition, this causal effect of BMI on BCC still remained (OR = 0.88; 95%CI,[- 0.22, - 0.03], p-value = 0.008) after adjusting for 25(OH)D level in the multivariable MR analysis. However, the results suggested that 25(OH)D level was not associated with BCC(OR = 1.02; 95%CI, [0.94,1.09], p-value = 0.67). In conclusion, similar to the conclusions of retrospective observational studies, the MR results indicate that high BMI is an independent protective factor for BCC. Meanwhile, vitamin D levels may not be causally associated with the risk of basal cell carcinoma and increasing vitamin D supplementation is unlikely to reduce the risk.